An Ex Vivo Model for the Onset of Human Labor

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Abstract
During gestation, the myometrium remains relaxed but undergoes a phenotypic transformation near term that initiates labor. This coincides with increased expression of contraction-associated proteins (CAPs) and decreased expression of relaxation-associated proteins (RAPs), thereby promoting the development of powerful synchronous contractions that deliver the fetus. We do not yet fully understand the biochemical signaling pathways and physiological changes that occur as human myometrium transitions from a non-laboring to a laboring phenotype. An ex vivo model for the onset of human labor can expand our knowledge. This study aimed to assess whether non-laboring pregnant human myometrium in culture undergoes a phenotypic transformation that is consistent with transitioning toward a labor-like phenotype. Term, non-laboring pregnant human myometrium biopsies were collected. A small portion was immediately snap-frozen (0 h time point), while the remaining tissue was dissected into small pieces, incubated for 48 h in serum-free medium, and then snap-frozen. Changes in the mRNA abundance of key myometrial genes were assessed by qRT-PCR, and protein levels were quantified by Western blotting. Data were analyzed using GraphPad Prism. Myometrial expression of key CAPs, including GJA1 , ESR1 , PTGS2 , NFκB1 , NFκB3 , IL1β , IL6 , and AKR1C1, increased significantly, while expression of the RAPs, PLCL1 , HSPB1 , and HSPB6 , was decreased significantly after 48 h of ex vivo culture. Term, non-laboring pregnant human myometrial explants undergo coordinated molecular remodeling during 48 h of ex vivo culture, with many changes paralleling those reported at term labor in vivo. These findings support prolonged explant culture as a model of the molecular transition toward a labor-like state, while also demonstrating that cultured non-laboring explants may no longer faithfully represent the original non-laboring phenotype.
Funding Information
  • The University of Newcastle

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